The study found that single-dose ethanol intoxication causes acute and long-lasting neuronal alterations in the brain.
Researchers from the Universities of Cologne, Mannheim, and Heidelberg have shown that even a single alcohol dose permanently changes the morphology of neurons. In particular, alcohol affects the synapses’ structure as well as the dynamics of the mitochondria, the cell’s powerhouses.
Professor Henrike Scholz and her team members Michèle Tegtmeier and Michael Berger demonstrated that alterations in the migration of mitochondria in the synapses lessen the rewarding effect of alcohol using the genetic model system of the fruit fly Drosophila melanogaster. These findings imply that even a single drinking incident might lay the foundation for alcohol addiction. The study was recently published in the journal Proceedings of the National Academy of Sciences.
What brain changes occur when sporadic drinking evolves into chronic alcohol abuse? That is the question explored by a collaborative research project including working groups from the Universities of Mannheim-Heidelberg and Cologne. The majority of scientific study has focused on the consequences of chronic alcohol drinking on the hippocampus, our brain’s control center.
Because of this, little is known about the acute neuronal interactions of critical risk factors, such as a first alcohol intoxication at an early age, explained Henrike Scholz: “We set out to discover ethanol-dependent molecular changes. These, in turn, provide the basis for permanent cellular changes following a single acute ethanol intoxication. The effects of a single alcohol administration were examined at the molecular, cellular, and behavioral levels.”
The working hypothesis was that a single administration of ethanol would create a positive connection with alcohol, similar to how memories are created after a single lesson.
The researchers used fruit flies and mouse models to test their theory and discovered ethanol-induced alterations in two areas: mitochondrial dynamics and the balance between synapses in neurons. Mitochondria supply energy to cells, particularly nerve cells. The mitochondria move in order to optimally deliver energy to the cells.
In the ethanol-treated cells, the mitochondria’s movement was disturbed. Certain synapses’ chemical balance was also disturbed. These alterations were permanent and were confirmed by behavioral changes in the animals: mice and fruit flies consumed more alcohol and relapsed later in life.
The morphological remodeling of neurons is a well-known basis for learning and memory. These so-called cellular plasticity mechanisms, which are central to learning and memory, are also thought to be at the core of the formation of associative memories for drug-related rewards.
Therefore, some of the observed morphological changes may influence ethanol-related memory formation. Together with the migration of mitochondria in neurons, which are also important for synaptic transmission and plasticity, the researchers speculate that these ethanol-dependent cellular changes are critical for the development of addictive behaviors.
“It is remarkable that the cellular processes contributing to such complex reward behavior are conserved across species, suggesting a similar role in humans,” said Henrike Scholz. “It could be a possible general cellular process essential for learning and memory.”
Both of the observed mechanisms could explain observations made in mice that a single intoxication experience can increase alcohol consumption and alcohol relapse later in life.
“These mechanisms may even be relevant to the observation in humans that the first alcohol intoxication at an early age is a critical risk factor for later alcohol intoxication and the development of alcohol addiction,” explained Professor Scholz. “This means that identifying lasting ethanol-dependent changes is an important first step in understanding how acute drinking can turn into chronic alcohol abuse.”
Reference: “Single-dose ethanol intoxication causes acute and lasting neuronal changes in the brain” by Johannes Knabbe, Jil Protzmann, Niklas Schneider, Michael Berger, Dominik Dannehl, Shoupeng Wei, Christopher Strahle, Michèle Tegtmeier, Astha Jaiswal, Hongwei Zheng, Marcus Krüger, Karl Rohr, Rainer Spanagel, Ainhoa Bilbao, Maren Engelhardt, Henrike Scholz and Sidney B. Cambridge, 14 June 2022, Proceedings of the National Academy of Sciences.